Complex compounds of aspartic acid with a rare earth metal and zinc

ABSTRACT

Complex compounds of aspartic acid with trivalent rare earths and zinc, and medical preparations consisting of or containing said compounds as effective agents in depressing the level of sugar in blood and urine. The invention also relates to a method of making the compounds.

Uite States tent [1 1 Evers [4 1 Aug. 12, 1975 t COMPLEX COMPOUNDS OF ASPARTIC ACID WITH A RARE EARTH METAL AND ZINC [76] Inventor: Walter Ever-s, Siemensstrasse 4,

2080 Pinneberg, Germany [22] Filed: Dec. 14, 1973 [21] Appl. No.: 425,060

[52] US. Cl 260/429.2; 424/289 [51] Int. Cl. C07F 3/06; CO7F 5/00 [58] Field of Search 260/429.2

[56] References Cited OTHER PUBLICATIONS Dreyer et al., Chem. Abs., Vol. 69, 100l4lq (1968).

Primary Examiner-Leland A. Sebastian Attorney, Agent, or Firm-A1lison C. Collard [5 7] ABSTRACT 6 Claims, N0 Drawings COMPLEX COMPOUNDS OF ASPARTIC ACID WITH A RARE EARTH METAL AND ZINC The present invention relates to complex compounds of aspartic acid with trivalent rare earths and zinc. It

also relates to medical preparations containing the complex compounds as efiective ingredients, and to a method of making the same.

It is known to influence the level of sugar in blood or urine by oral administration of sulfonyl derivatives and products based upon biguanides, as well as similar medication with substances obtained by total extraction of vegetables, e.g., bean peels. It is further known from German Pat. No. 936,592 that similar effects may be obtained by compounds of rare earths with parts of plants containing glycosides of trihydroxyflavones.

It was found quite unexpectedly that complex compounds of aspartic acid with trivalent rare earths and zinc are particularly effective in depressing the level of blood sugar and urine sugar.

It is therefore an object of the present invention to prepare complex compounds of aspartic acid with trivalent rare earths and zinc, and to use them in medical preparations as a depressant for sugar in blood and urine. The preferred rare earth is cerium or praseodymium; the preferred aspartic acid is l-aspartic acid. It is assumed that in the compounds according to the invention, the acidic hydrogen of aspartic acid is substituted by the metal and that a complex formation occurs between the amino group and the rare earth. The invention also relates to preparations which contain or consist of one or several of the described compounds as effective agents.

It was further found that these complex compounds are capable of highly increasing the effects of the abovementioned trihydroxyflavones. According to one embodiment of the invention, medical preparations are claimed which contain as effective agents, one or more complexes of trihydroxyflavone with a trivalent rare earth.

The invention also relates to a process for making the compounds according to the invention which comprises the following steps:

The amino nitrogen of aspartic acid is converted into an ammonium salt. To this salt is then added the double salt of the trivalent rare earth and zinc by complex formation, with sodium peroxide added as a catalyst. In further steps, the addition compound is precipitated with sodium hydroxide solution and crystallized by the addition of 77 percent alcohol.

More particularly, the process may be carried out as follows:

The starting material, aspartic acid, is hydrolysed by addition of e.g. HCl, whereby in a manner known per se, the ammonium salt is formed (NI-I being intermediately formed from the amino nitrogen). By the presence of the ammonium ions, a basis is given for later formation of complex compounds.

In the next step, the double salts of trivalent rare earth and zinc are added to the acidic hydrolysate, while heating in the presence of the catalyst sodium peroxide. The complexes formed in analogy to the preparation of glycine-copper are precipitated in the cold at the isoelectric point in the neutral range with sodium hydroxide solution, and subsequently washed with 77 percent ethanol, and dried.

The carbonates of cerium and praseodymium and the sulfate of zinc proved to be especially suitable for reasons of easy handling and good yields.

In the following, the invention is more fully described by two examples which are given by way of illustration and not of limitation.

EXAMPLE 1 532.4 g of l-aspartic acid in 500 cc of distilled water and 600 cc of 37 percent HCl were hydrolysed with simultaneous conversion of the amino nitrogen into an ammonium salt. Thereafter, 550.37 g cerium carbonate and 161.44 g zinc sulfate were added, and the mixture heated to 40C, after addition of 0.1 g sodium peroxide as catalyst.

The so obtained solution was cooled to 30C after filtration from impurities in the cerium carbonate, if any; then 15 cc of 20 percent sodium hydroxide solution were added at room temperature. The precipitate which formed was separated by filtration and washed with 77 percent alcohol. Washing was repeated three times.

The residue obtained was dried at 40C in an oven; it is the cerium/zinc/aspartate complex. The yield amounted to about 850 g, the crystalline mass having a melting point of 243.5C and a molecular weight of 994.21.

EXAMPLE 2 The process was carried out as described in Example 1. However, instead of using cerium, praseodymium was used while the starting material was again 1- aspartic acid.

While the invention has been illustrated in two examples only, it should be understood that many modifications can be applied in the particulars without departing from the spirit of the invention and the scope of the following claims.

What is claimed is: 1. A complex compound of aspartic acid with a rare earth and zinc.

2. The. complex compound as recited in claim 1, wherein the rare earth is cerium.

3. The complex compound as recited in claim 1, wherein the rare earth is praseodymium.

4. A method of preparing a complex compound of aspartic acid with a rare earth and zinc, which comprises the steps of converting the amino nitrogen of aspartic acid into an ammonium salt;

adding a double salt to a trivalent rare earth and of zinc while using sodium peroxide as catalyst, thereby forming said complex salt; and

precipitating the complex compound with sodium hydroxide and crystallizing the compound by washing with alcohol.

5. The method as recited in claim 4, wherein step 2 is carried out with the carbonate of cerium or praseodymium and the sulfate of zinc.

6. The method as recited in claim 4 additionally comprising the step of drying the precipitate. 

1. A COMPLEX COMPOUND OF ASPARTIC ACID WITH A RARE EARTH AND ZINC.
 2. The complex compound as recited in claim 1, wherein the rare earth is cerium.
 3. The complex compound as recited in claim 1, wherein the rare earth is praseodymium.
 4. A method of preparing a complex compound of aspartic acid with a rare earth and zinc, which comprises the steps of converting the amino nitrogen of aspartic acid into an ammonium salt; adding a double salt to a trivalent rare earth and of zinc while using sodium peroxide as catalyst, thereby forming said complex salt; and precipitating the complex compound with sodium hydroxide and crystallizing the compound by washing with alcohol.
 5. The method as recited in claim 4, wherein step 2 is carried out with the carbonate of cerium or praseodymium and the sulfate of zinc.
 6. The method as recited in claim 4 additionally comprising the step of drying the precipitate. 